Probiotics and Antimicrobial Proteins最新文献

Research into the role of probiotics-often referred to as "living supplements"-in cancer therapy is still in its early stages, and uncertainties regarding their effectiveness remain. Relevantly, chemopreventive and therapeutic effects of probiotics have been determined. There is also substantial evidence supporting their potential in cancer treatment such as immunotherapy. Probiotics employ various mechanisms to inhibit cancer initiation and progression. These include colonizing and protecting the gastrointestinal tract (GIT), producing metabolites, inducing apoptosis and autophagy, exerting anti-inflammatory properties, preventing metastasis, enhancing the effectiveness of immune checkpoint inhibitors (ICIs), promoting cancer-specific T cell infiltration, arresting the cell cycle, and exhibiting direct or indirect synergistic effects with anticancer drugs. Additionally, probiotics have been shown to activate tumor suppressor genes and inhibit pro-inflammatory transcription factors. They also increase reactive oxygen species production within cancer cells. Synergistic interactions between probiotics and various anticancer drugs, such as cisplatin, cyclophosphamide, 5-fluorouracil, trastuzumab, nivolumab, ipilimumab, apatinib, gemcitabine, tamoxifen, sorafenib, celecoxib and irinotecan have been observed. The combination of probiotics with anticancer drugs holds promise in overcoming drug resistance, reducing recurrence, minimizing side effects, and lowering treatment costs. In addition, fecal microbiota transplantation (FMT) and prebiotics supplementation has increased cytotoxic T cells within tumors. However, probiotics may leave some adverse effects such as risk of infection and gastrointestinal effects, antagonistic effects with drugs, and different responses among patients. These findings highlight insights for considering specific strains and engineered probiotic applications, preferred doses and timing of treatment, and personalized therapies to enhance the efficacy of cancer therapy. Accordingly, targeted interventions and guidelines establishment needs extensive randomized controlled trials as probiotic-based cancer therapy has not been approved by Food and Drug Administration (FDA).

With the in-depth and comprehensive research on probiotic Bacillus, it has become a hot topic in food science. However, the current status of research using bibliometric analysis to assess the application of probiotic Bacillus in food science has not been comprehensively reviewed. The Web of Science (WOS) database was used in this review's bibliometric analysis to determine the hotspots for research as well as the extent of completed experiments. Furthermore, a systematic review was conducted on the research hotspots of probiotic Bacillus in food science. The comprehensive analysis showed it was a growing and global research field. The keywords with high frequency mainly included "spore," "strain," and "production," which were research hot topics in the last decade. The application of the spore form or nutrient cells of probiotic Bacillus in industrialized food production through nutrient fortification, fermentation agents, and highly efficient synthesis of metabolites showed great development potential.

Notwithstanding the indefatigable endeavors to develop effective anti-mycobacterial therapies, mycobacterial infections still present a tough problem for medicine today. The problem is further complicated by the disquieting surge of drug-resistant mycobacterial pathogens, which considerably narrows the existing therapeutic options. Thus, there is a genuine need to discover novel anti-mycobacterial drugs. Animal venoms are considered a treasure trove of structurally variable and biologically active peptides, which may hold promise for therapeutic applications. Over the past two decades, abundant evidence has been amassed regarding anti-mycobacterial effects of various peptides derived from the venoms of honeybees, wasps, scorpions, pseudoscorpions, cone snails, and snakes. This review intends to consolidate the state-of-the-art knowledge on the anti-mycobacterial peptides of animal venoms and to sketch potentially fruitful directions for future investigations. The available data indicate that micromolar concentrations of particular venom-derived peptides can effectively inhibit the in vitro growth of Mycobacterium tuberculosis and non-tuberculous mycobacteria. The proposed mechanisms of action of venom-derived peptides include reduced activity of plasma membrane ATPase, depolarization of the cell membrane, disruption of the cell wall, and increased generation of reactive oxygen species. Interestingly, administering certain peptides (≤ 2 mg/kg body weight) through daily intraperitoneal injections to mice for 8 consecutive days resulted in lower levels of mycobacterial infections and inflammation, hitting two targets with one arrow. Indubitably, such peptides can usher in new possibilities for the prevention and treatment of recalcitrant mycobacterial infections.

Human β-defensin (HBD) has been recognized as a promising antimicrobial agent due to its broad-spectrum antimicrobial activity against various pathogens. In our previous work, we engineered a chimeric human β-defensin, designated H4, by fusing human β-defensin 3 and human β-defensin 4, resulting in enhanced antimicrobial activity and salt stability. However, the high cost of chemical synthesis due to the relatively large number of amino acids in H4 has limited its applications. To reduce production costs, we aimed to develop an alternative method using a prokaryotic expression system. We first optimized the codon usage of the H4 gene for prokaryotic expression and then cloned it into the pET32a vector, incorporating thioredoxin and enterokinase cleavage sites to minimize toxicity in host cells. The resulting plasmid was transformed into E. coli BL21, yielding a fusion protein (TrxA-EK-H4). Correct cleavage of TrxA-EK-H4 required the addition of urea as a denaturant in the dialysis buffer. However, on-column enzymatic cleavage obviated the need for denaturants and yielded higher-purity rH4. The antibacterial activity of rH4 against multidrug-resistant Acinetobacter baumannii was comparable to that of chemically synthesized H4. This study demonstrates a valuable strategy for efficient purification of challenging proteins and has significant implications for future biotechnological applications.

Women's health is related to several factors that include physical, mental, and reproductive health. Additionally, the vaginal microbiota modulation performs a fundamental role in the regulation of physiological homeostasis and dysbiosis, which provides us a potential overview of the use of different biotic agents and their implications for female health. The objective of this work was propitiated insights and conception about the influence of probiotics, prebiotics, synbiotics, and postbiotics as adjuvants for prevention/treatment on the main infections that can affect women's health. Therefore, seventy-one studies published in the Web of Science Core Collection database from 1999 to 2024 were evaluated and performed to a bibliometric analysis employing the VOSviewer software for scientific mapping and network analysis. Our results suggest that administration of biotic agents as adjuvants are relevant for the prevention and/or treatment of the main diseases that affect female health, since they contribute to a healthy vaginal microbiota through anti-inflammatory and antimicrobial activities. Most clinical studies have demonstrated the effectiveness of intervention using probiotics to the detriment of other biotic agents in women's health, being bacterial vaginosis, polycystic ovary syndrome, and vulvovaginal candidiasis, the main diseases evaluated. However, preclinical studies have emphasized that the inhibition of pathogens responsible for the process of vaginal dysbiosis may be due to the formation of biofilm and the synthesis of compounds that could prevent the adhesion of these microorganisms. Future perspectives point to the beneficial modulation of the vaginal microbiota by biotic agents as a promising adjuvant approach to improve women's health.

Probiotics are live microorganisms that confer health benefits to humans, offering significant potential for preventing and treating various diseases. Neurological disorders, driven by multifaceted factors and linked to high disability rates, have become a growing global concern, particularly in the context of an aging population. Recent studies emphasize a strong connection between dysbiosis of the gut microbiota and neurological disorders. Probiotics have emerged as promising therapeutic interventions due to their ability to modulate the gut microbiota and influence the production of key metabolites, such as short-chain fatty acids and neurotransmitters, crucial for neurological health. However, probiotic viability is often compromised, limiting their therapeutic efficacy. We propose that developing high-activity probiotic formulations, coupled with innovative delivery strategies, holds considerable promise for advancing neurological treatments. Encapsulation systems have proven effective in enhancing probiotic stability and efficacy. This review discusses advances in probiotic delivery using biological macromolecule-based encapsulation, addressing key challenges in maintaining viability during production, storage, and digestion. It also highlights emerging delivery systems, such as microencapsulation, aimed at improving stability and therapeutic effectiveness. Additionally, the review explores the potential of functional foods enriched with probiotics for neurological health. Future research should explore clinical applications of encapsulated probiotics and support the development of functional foods to enhance neurological health.

The emergence of multidrug-resistant pathogens presents a significant global health challenge, which is primarily fuelled by overuse and misuse of antibiotics. Bacteria-derived antimicrobial metabolites offer a promising alternative strategy for combating antimicrobial resistance issues. Bacillus velezensis PD9 (BvPD9), isolated from stingless bee propolis, has been reported to have antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA). This study aimed to characterise and identify the antimicrobial compounds (AMCs) synthesised by BvPD9 through integration of genome mining and liquid chromatography-mass spectrometry (LC-MS) analysis. The whole-genome sequence of BvPD9 contained 4,263,351 base pairs and 4101 protein-coding sequences, with 12 potential AMC biosynthetic gene clusters. Comparative genomic analysis highlighted the unique profile of BvPD9 that possesses the largest number of unknown proteins, indicating significant potential for further exploration. The combined genomics-metabolic profiling uncovered five AMCs in BvPD9 extract, including bacillibactin, bacilysin, surfactin A, fengycin A, and bacillomycin D. The extract exhibited a broad antibacterial spectrum against 25 pathogenic bacteria, including both Gram-positive and Gram-negative bacteria, with the lowest minimum inhibitory concentration (MIC, 0.032 mg/ml) against S. epidermidis ATCC 12228, and the lowest minimum bactericidal concentration (MBC; 0.128 mg/ml) against MRSA ATCC 700699 and Aeromonas hydrophilia. The robust stability of BvPD9 extract was demonstrated at high temperatures, over a wide range of pH conditions (6 to 12) and in the presence of various hydrolytic enzymes. Additionally, the extract showed 50% haemolytic and cytotoxicity activity at 0.158 and 0.250 mg/ml, respectively. These characteristics suggest potential applications of BvPD9 metabolites for tackling antimicrobial resistance and its applicability across diverse industries.

Recent evidence links gut microbiota alterations to neurodegenerative disorders, including Parkinson's disease (PD). Replenishing the abnormal composition of gut microbiota through gut microbiota-based interventions "prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT)" has shown beneficial effects in PD. These interventions increase gut metabolites like short-chain fatty acids (SCFAs) and glucagon-like peptide-1 (GLP-1), which may protect dopaminergic neurons via the gut-brain axis. Neuroprotective effects of these interventions are mediated by several mechanisms, including the enhancement of neurotrophin and activation of the PI3K/AKT/mTOR signaling pathway, GLP-1-mediated gut-brain axis signaling, Nrf2/ARE pathway, and autophagy. Other pathways, such as free fatty acid receptor activation, synaptic plasticity improvement, and blood-brain and gut barrier integrity maintenance, also contribute to neuroprotection. Furthermore, the inhibition of the TLR4/NF-кB pathway, MAPK pathway, GSK-3β signaling pathway, miR-155-5p-mediated neuroinflammation, and ferroptosis could account for their protective effects. Clinical studies involving gut microbiota-based interventions have shown therapeutic benefits in PD patients, particularly in improving gastrointestinal dysfunction and some neurological symptoms. However, the effectiveness in alleviating motor symptoms remains mild. Large-scale clinical trials are still needed to confirm these findings. This review emphasizes the neuroprotective mechanisms of gut microbiota-based interventions in PD as supported by both preclinical and clinical studies.

European foulbrood (EFB) is a bee larvae-specific infectious disease and the causative pathogen is Melissococcus plutonius. Broad-spectrum antibiotics have classically been used in many countries to control the pathogens; however, their use in apiaries was discontinued in several countries due to concerns regarding the health of bees and humans. Therefore, the development of alternative treatments for use in apiaries that are safe for bees and humans is essential. The present study examined the effects of nisin A supplementation using artificially reared honey bee larvae infected by M. plutonius strains. The results obtained showed that a non-purified nisin A product was toxic to honey bee larvae, while semi-purified nisin A by removing low-molecular-weight (< 3,000) chemicals was not lethal to honey bee larvae. A larval diet supplemented with the semi-purified nisin A significantly increased the survival rate of larvae infected by M. plutonius. The levels of nisin A required for this rescue differed between the M. plutonius strains used for infection, and 12.5 and 100 µg/mL were required for strain DAT606 belonging to clonal complex 3 and strain DAT561 belonging to clonal complex 12, respectively. This beneficial effect was attributed to the antagonistic activity of nisin A against M. plutonius strains, and the levels of viable M. plutonius strains significantly decreased in the larval gut at the required concentrations. Due to the risks associated with the use of antibiotics in apiaries, food-grade nisin A is a promising alternative to control EFB.

This review paper delves into the role of probiotics and food bioactives in influencing gut health and overall well-being, within the context of probiotics and food bioactives, emphasizing their roles in modulating inflammation, gut microbiota, and metabolic health. Probiotics are defined as live microorganisms that confer health benefits to the host, primarily through their impact on the gut microbiome; a complex community of microorganisms crucial for maintaining health. The review aims to elucidate how probiotics, incorporated into both traditional and modern food systems, can enhance gut health and address metabolic disorders. It examines the types of probiotics present in various foods and their mechanisms of action, including their effects on immune function and metabolic health. By exploring the links between probiotics and health outcomes such as digestive health, immune support, and mental health, the review identifies specific conditions where probiotics show significant promise. Hurldes such as inconsistencies in research findings, variability in probiotic strains, and dosages are addressed. The paper also suggests future research directions, including the potential for personalized probiotic interventions. The review concludes by summarizing key findings and emphasizing the critical role of probiotics in food systems for promoting overall health and mitigating metabolic diseases.